Neuroprotective effects of clavulanic acid following permanent bilateral common carotid artery occlusion in rats.

Abstract

We investigated whether clavulanic acid could improve learning and memory, in rats underwent bilateral occlusion of common carotid artery (2VO). Seventy male Wistar rats were subjected to 2VO, with a 1-week interval between right and left artery occlusions. After 2VO, animals received clavulanic acid (10, 20, 40 mg/kg, intraperitoneally), from day 8 to 20. Spatial memory was assessed in the Morris water maze, 1 week after the induction of 2VO (day 15). The mRNA expression levels of bcl-2, bcl2-associated x protein (bax), caspase-3, inducible nitric oxide synthase (iNOS), and amyloid beta precursor protein (APP) were measured in the neocortex and hippocampus. Clavulanic acid significantly decreased the escape latency and swimming time in the training trial days. As well, it increased time and distance percentage in the target quadrant, while it decreased such factors in the opposite quadrant in the final trial day, compared to 2VO + normal saline animals. Real time-PCR data showed a significant higher mRNA expression of bax, caspase 3, and iNOS in the hippocampus and neocortex of 2VO animal compared to nonoccluded rats. APP increased in the neocortex but not hippocampus. Compared with 2VO animals, clavulanic acid significantly down-regulated the expression of iNOS, caspase 3, and APP, accompanied by diminishing the bax/bcl2 ratio. Our results reveal a potential therapeutic use of clavulanic acid for cognitive dysfunction associated with cerebral hypoperfusion in vascular dementia and Alzheimer disease.

• Authors: Mustafa Ghanbarabadi, Farahnaz Falanji, Abolfazl Rad, Nafiseh Chazani Sharahi, Sakineh Amoueian, Mohamadreza Amin, Mehdi Molavi, Bahareh Amin
• Journal: Drug development research (Drug Dev Res) Vol. 80 Issue 8 Pg. 1110-1119 (12 2019) ISSN: 1098-2299 [Electronic] United States
• PMID: 31482584 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Wiley Periodicals, Inc.

Chemical References

• Bax protein, rat
• Neuroprotective Agents
• bcl-2-Associated X Protein
• Clavulanic Acid
• Nitric Oxide Synthase Type II
• Nos2 protein, rat
• Casp3 protein, rat
• Caspase 3

Topics

• Animals
• Arterial Occlusive Diseases (complications, etiology)
• Carotid Artery, Common
• Caspase 3 (genetics)
• Clavulanic Acid (administration & dosage, pharmacology)
• Dementia, Vascular (drug therapy, etiology)
• Disease Models, Animal
• Gene Expression Regulation (drug effects)
• Hippocampus (drug effects, metabolism)
• Male
• Neocortex (drug effects, metabolism)
• Neuroprotective Agents (administration & dosage, pharmacology)
• Nitric Oxide Synthase Type II (genetics)
• Rats
• Rats, Wistar
• Spatial Memory (drug effects)
• bcl-2-Associated X Protein (genetics)